The goal of this work is to use methods of cell and molecular genetics to test the hypothesis that differentiated traits responsive to 5-bromodeoxyuridine (BrdU) are under physiological control of one or a few regulatory gnees, and that disruption of this gene program results in altered antigenicity and suppressed tumorigenicity in the melanoma cell system under study. I will test the capacity of chemicals having clearly defined mechanisms of action to promote re-expression of differentiated phenotypes suppressed by BrdU, and will thus attempt to gain further insight into mechanisms of melanoma cell differentiation. I will use DNA-mediated gene transformation as an assay for hypothesized pleiotropic effects of single genes on BrdU-responsive traits. As a means of studying the role of retrovirus in immunogenicity of nontumorigenic, BrdU-grown melanoma cells I will isolate mutants deficient in retrovirus production. I will use genetic, biochemical and immunochemical methods in order to gain knowledge of basic mechanisms underlying normal differentiation and neoplasia and the underlying cause of tumor rejection of cells altered by growth with BrdU. This knowledge could lead to new approaches in cancer therapy.